Petitou M, Duchaussoy P, Lederman I, Choay J, Sinaÿ P
Institut Choay, Paris, France.
Carbohydr Res. 1988 Aug 15;179:163-72. doi: 10.1016/0008-6215(88)84116-8.
Known methyl (prop-1-enyl 2,3-di-O-benzyl-alpha-D-glucopyranosid)uronate was first converted into methyl (prop-1-enyl 2,3-di-O-benzyl-4-O-levulinyl-alpha-D-gluco-pyranosid)uro nat e. Acid hydrolysis, followed by treatment with (bromomethylene)-dimethylammonium bromide, gave methyl (2,3-di-O-benzyl-4-O-levulinyl-alpha-D-glucopyranosyl bromide)uronate. Condensation of this bromide with 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranose gave 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-(methyl 2,3-di-O-benzyl-4-O- levulinyl-beta-D-glucopyranosyluronate)-beta-D-glucopyranose. Acetolysis, followed by selective anomeric O-deacetylation and treatment with (bromomethylene)dimethylammonium bromide then gave 6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-4-O-(methyl 2,3-di-O-benzyl-4-O-levulinyl -beta-D-glucopyranosyluronate)-alpha-D-glucopyranosyl bromide. Condensation of this bromide with benzyl 6-O-acetyl-3-O-benzyl-2-benzyloxycarbonylamino-2-deoxy-4- O-(methyl 2-O-acetyl-3-O-benzyl-alpha-L-idopyranosyluronate)-alpha-D- glucopyranoside provided benzyl O-(methyl 2,3-di-O-benzyl-4-O-levulinyl-beta-D- glucopyranosyluronate)-(1----4)-O-(6-O-acetyl-2-azido-3-O-benzyl-2-deoxy - alpha-D-glucopyranosyl)- (1----4)-O-(methyl 2-O-acetyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)- 6-O-acetyl-3-O-benzyl-2-benzyloxycarbonylamino-2-deoxy-alpha-D-glu copyranoside. Removal of the levulinyl group followed by condensation with 6-O-acetyl-2-azido-3,4-di-O -benzyl-2-deoxy-alpha-D-glucopyranosyl bromide provided benzyl O-(6-O-acetyl-2- azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2,3-di- O-benzyl-beta-D-glucopyranosyluronate)-(1----4)-O-(6-O-acetyl-2-azido-3- O- benzyl-2- deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2-O-acetyl-3-O-benzyl-alpha-L- idopyranosyluronate)-(1----4)-6-O-acetyl-3-O-benzyl-2-benzyloxycarbon ylamino-2- deoxy-alpha-D-glucopyranoside in 78% yield. O-Deacetylation followed by re-esterification, O-sulfation, catalytic hydrogenolysis, saponification, and N-sulfation gave the non-sodium salt of O-(2-deoxy-6-O-sulfo-2-sulfoamino-alpha-D-glucopyranosyl)-(1----4) -O- (beta-D-glucopyranosyluronic acid)-(1----4)O-(2-deoxy-6-O-sulfo-2-sulfoamino- alpha-D-glucopyranosyl)-(1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)- (1----4)-2-deoxy-6-O-sulfo-2-sulfoamino-D-glucopyranose. This synthetic pentasaccharide neither binds to antithrombin III nor induces anti-factor Xa activity.
已知的甲基（1-丙烯基 2,3-二-O-苄基-α-D-吡喃葡萄糖苷）uronate 首先被转化为甲基（1-丙烯基 2,3-二-O-苄基-4-O-乙酰丙酮基-α-D-吡喃葡萄糖苷）uronate。酸水解，随后用（溴亚甲基）二甲基溴化铵处理，得到甲基（2,3-二-O-苄基-4-O-乙酰丙酮基-α-D-吡喃葡萄糖基溴）uronate。该溴化物与 1,6-脱水-2-叠氮基-3-O-苄基-2-脱氧-β-D-吡喃葡萄糖缩合得到 1,6-脱水-2-叠氮基-3-O-苄基-2-脱氧-4-O-（甲基 2,3-二-O-苄基-4-O-乙酰丙酮基-β-D-吡喃葡萄糖醛酸基）-β-D-吡喃葡萄糖。乙酰解，随后进行选择性异头 O-脱乙酰化并使用（溴亚甲基）二甲基溴化铵处理，然后得到 6-O-乙酰基-2-叠氮基-3-O-苄基-2-脱氧-4-O-（甲基 2,3-二-O-苄基-4-O-乙酰丙酮基-β-D-吡喃葡萄糖醛酸基）-α-D-吡喃葡萄糖基溴。该溴化物与苄基 6-O-乙酰基-3-O-苄基-2-苄氧羰基氨基-2-脱氧-4-O-（甲基 2-O-乙酰基-3-O-苄基-α-L-吡喃艾杜糖醛酸基）-α-D-吡喃葡萄糖苷缩合得到苄基 O-（甲基 2,3-二-O-苄基-4-O-乙酰丙酮基-β-D-吡喃葡萄糖醛酸基）-（1→4）-O-（6-O-乙酰基-2-叠氮基-3-O-苄基-2-脱氧-α-D-吡喃葡萄糖基）-（1→4）-O-（甲基 2-O-乙酰基-3-O-苄基-α-L-吡喃艾杜糖醛酸基）-（1→4）-6-O-乙酰基-3-O-苄基-2-苄氧羰基氨基-2-脱氧-α-D-吡喃葡萄糖苷。去除乙酰丙酮基，随后与 6-O-乙酰基-2-叠氮基-3,4-二-O-苄基-2-脱氧-α-D-吡喃葡萄糖基溴缩合，得到苄基 O-（6-O-乙酰基-2-叠氮基-3,4-二-O-苄基-2-脱氧-α-D-吡喃葡萄糖基）-（1→4）-O-（甲基 2,3-二-O-苄基-β-D-吡喃葡萄糖醛酸基）-（1→4）-O-（6-O-乙酰基-2-叠氮基-3-O-苄基-2-脱氧-α-D-吡喃葡萄糖基）-（1→4）-O-（甲基 2-O-乙酰基-3-O-苄基-α-L-吡喃艾杜糖醛酸基）-（1→4）-6-O-乙酰基-3-O-苄基-2-苄氧羰基氨基-2-脱氧-α-D-吡喃葡萄糖苷，产率为 78%。O-脱乙酰化，随后进行重新酯化、O-硫酸化、催化氢解、皂化和 N-硫酸化，得到 O-（2-脱氧-6-O-磺基-2-磺氨基-α-D-吡喃葡萄糖基）-（1→4）-O-（β-D-吡喃葡萄糖醛酸）-（1→4）O-（2-脱氧-6-O-磺基-2-磺氨基-α-D-吡喃葡萄糖基）-（1→4）-O-（2-O-磺基-α-L-吡喃艾杜糖醛酸）-（1→4）-2-脱氧-6-O-磺基-2-磺氨基-D-吡喃葡萄糖的非钠盐。这种合成的五糖既不与抗凝血酶 III 结合，也不诱导抗因子 Xa 活性。
